Pathology - Zafar Flashcards
Breast Embryology
- largest skin gland: modified sweat gland
- at the end of first month, a solid bud develops and invaginates into underlying mesenchyme
- primary bud gives off several secondary buds that develop into lactiferous ducts which branch off further to form mammary gland
- during pregnancy the breast assumes it’s complete morphologic and functional maturity
Breast Anatomy
- symmetric double organ
- reaches normal size b/w 16-19 yrs
- b/w 2nd & 6th ribs and sternum and axilla
- nipple & areola, superficial skin
- breast is divided into 10-20 lobes, each lobe (lobules: ducts+acini=TDLU)
- embedded in stroma
Breast Pathology: Classification
congenital or acquired
Accessory Breast Tissue
- in axillary fossa
- tumors here may be confused with ax. LN or mets
Ectopic Breast Tissue
- may develop along mammary line
- failure of any portion of mammary ridge to involute
Macromastia
-excessive breast tissue
Nipple Inversion
- associated with large pendulous breasts
- may be confused with CA
Supernumerary Breast/Nipples
-persistent epidermal thickenings along milk line from axilla to perineum
Acute Mastitis/Abscess
non-neoplastic-acquired
- tender, associated with lactation
- cracks in nipple
- staph and strep (pyogenic bacteria)
Silicone Implants
non-neoplastic-acquired
- for a fibrous capsule (synovial metaplasia)
- gel may seep through intact implant shells
Fibrocystic Changes/Disease of Breast
non-neoplastic-acquired
- considered a hyperplastic disorder
- proliferative vs. nonproliferative (cystic)
- women 25-45 (hormonal imbalance?)
- decreased risk with OTC
- increased mitotic and apoptotic rate
- may hamper adequate/optimal mammography
Sclerosing Adenosis
~30 y/o
- risk of CA 1.5-2x normal
- associated with clustered microcal
- low power diagnosis
- rarely involved by LCIS
- -if palpable called adenosis tumor
- retains lobular architecture
- 2 cell-layered
- actin immunohistochemistry + (myoepithelial cells)
- related lesion-Radial Scar
Atypical Ductal Hyperplasia
- features suggestive but not diagnostic of DCIS
- increased risk of carcinoma 2-4x5 times
- rick equal in both breast-maybe multicentric
- multilayering of cells with progressive loss of nuclear polarity, enlarged nuclei, and nucleoli
- most authors require 2+ involved ducts to call DCIS
- loss of heterozygosity to 16q (40% clonal)
Atypical Lobular Hyperplasia (ALH)
- resembles LCIS but does not fill or distend 50% or more acini within a lobule
- has focal preservation of luminal spaces
- 4x5 usual risk of CA in either breast (greater in pre-menopausal)
Fibroadenoma
-most common benign tumor (breast mouse)
~20-35 age women (younger)
-Fibradenomatosis
-may have a neoplastic stromal component with polyclonal epithelial component
-hormonally responsive: may grow in pregnancy
-malignant transformation <0.1%
Fibroadenomatosis
-multifocal disease in post renal transplant and with EBV in immunosuppressed
Fibroadenoma: Gross Appearance
- sharply circumscribed
- freely mobile
Fibroadenoma: Microscopic
- stromal & epithelial component
- glandular epithelium without atypia
- myoepithelial cells are present
- stroma generally not very cellular (dd Phyllodes) but may have other stromal elements like cartilage, muscle
- coexisting features: fibrocysitc change, sclerosing adenosis
- FNAC very helpful in regular variant
Large Duct Papilloma
- 48y/o, solitary, close to nipple-lactiferous ducts & sinuses
- 1.5-2x risk of cancer, colonal
- serous/bloody nipple dischargee (80%), nipple retraction may be present
Large Duct Papilloma: Gross
- <3cm
- soft
- hemorrhagic
Fibroadenoma: Juvenile/Giant cell variant
-adolescent, often bilateral, often very large and may have very cellular stroma and glands (dd phyllodes tumor)
Large Duct Papilloma: Microscopic
- multiple papillae in complex arborizing pattern
- calcification possible
- myoepithelium present (S1000+)
- malignant if severe atypia, abnormal mitosis, single cell layered, pseudostradification no vascular core or cribriform morphology
Large Duct Papilloma: Treatment
-surgical excision
Fat Necrosis
- trauma: patient may not give history
- Generally related to lactation, pregnancy, or sports activity
- may present as ill-defined mass
- may show calcification
- may cause puckering of skin
- DD-carcinoma
Gynecomastia
- enlargement of male breast: hypertrophy & hyperplasia
- increased estrogen to androgen ratio
- puberty: alcohol, cirrhosis, drugs
- button or disc-like stromal enlargement
- periductal stromal edema or fibrosis “Halo” effect
Genetics of Breast Cancer?
- first degree relatives at increased risk
- higher if relative has bilateral disease, early incidence in relative or >1 relative affected
- heterogenous carriers for ataxia-telangiectasia
Li-Fraumeni syndrome
germline p53 mutations
-25% patients effected
BCRA 1 & 2
1 (17q21) 2 (13q12) -tumor supressor genes involved in familial cancer -5-10% of breast cancer cases -1% of general population
Cowden Disease
- multiple hemartoma syndrome
- 10q mutation
- much increased risk
Breast Cancer: Hormonal
increased risk:
- early menarche
- late menopause
- nulliparity
- having first child after 30
- recent use of oral contraceptives
- HRT (estrogen + progesterone) in postmenopausal women
- physical inactivity
- consumption of 1 or more alcoholic/day
- postmeno. w/obesity or estrogen producing ovarian tumor
Breast Cancer: Environmental
- US > Japan/Taiwan (5:1), also N. Europe, fatty diet & heavy alcohol use
- not associated with smoking
- in blacks: higher stage, high nuclear grade, higher mortality rate, more frequent in women <40, more likely ER/PR negative
Breast Cancer: Hormonal Receptors
-ER/PR - response to anti-estrogen therapy (Tamoxifen) and prognosis
Breast Cancer: Local Spread
- skin
- nipple
- chest wall
Breast Cancer: Nodal Mets
- axilla
- supraclavicular
- internal mammary
Breast Cancer: Distant Mets
- skeletal system
- liver
- lung/pleura
- ovary
- adrenal
- CNS
- lobular CA favors abdominal cavity/viscera*
Breast Cancer: Treatment
- surgery (lumpectomy/mastectomy)
- radiation
- chemotheraphy
- anti-estrogen
- Herceptin
Breast Cancer: Histological Grading
-score of 3-9 Modified Bloom and Richardson System
Breast Cancer: Her2 (c-erbB2)
- overexpression with gene amplification
- aggressive tumor behavior
- IHC and FISH 0-3+
- membranous staining
Breast Cancer: Prognostic Factors
- stage
- tumor size
- histologic grade
- ax LN status
- age <50 better
- histologic type (tubular, cribriform, medullary (better), signet ring, inflammatory (worse))
- skin invasion
- nipple inversion
- angiolymphatic invasion
- fibrotic focus
Breast Cancer: Predictive Variables
- ER/PR & Her2 Status
- ploidy & S-phase fraction have no predictive value
Breast Cancer: Axillary Lymph Node
-involvement most improtant prognostic factor for disease (free & overall survival & Rx regimen)
Breast Cancer: Sentinel Lymph Nodes
- first lymph node that receives breast drainage/mets
- usually ventral group (level 1)
- replacement for axillary dissection in T1 & T2 tumors
- cluster size of 0.2-2mm may indicate significant axillary dz.
Breast Cancer: Core Biopsy
- alternative to open biopsy
- large (14 gage 1st gen or 11g 2nd gen)
- computer (stereostactic) or US guided
Breast Cancer: FNAC
90% sensitive, 95% specific
- fibrotic areas difficult to aspirate
- false neg small tumors, tubular CA, cribriform CA
- false + w/florid ductal hyperplasia
- neg FNA with lingering suspicion - BX
Breast Cancer: Frozen Section
-real time evaluation in surgery
In-Situ
-stromal invasion is not seen
Ductal Carcinoma in situ
-tumor confined to glandular component - no stromal invasion, BM intact
-tumor can spread along ducts
-4x more common than LCIS
-15-30% of all cancer - mammography
-assoc. with development of invasive cancer at or near the site
-Rx: surgery + radiation
-cytologic features for grading: low vs. high grade
low (0-10%) high (40%) progress
Lobular Carcinoma in situ
- generally incidental: no distinguishing features at gross exam and no microcal
- 50-70% bilateral (vs. 10% for DCIS)
- 75% multicentric
- 30% risk of invasive disease in either breast (relative risk 9x normal) Invasive dz may be of ductal or lobular type
- 5% have coexisten invasive cancer
- lobular cancerization of ducts
- minimal risk of dying from cancer if periodically examined
- rx: watchful waiting vs. ip/bil mastectomy
Comedo Carcinoma (DCIS Variant)
- 1/3 multicentric, 10% bilateral
- 40% progressive (invasive)
- some patient have axillary mets
- high grade cells with central necrosis
- Her2 amplification, p53 mutation positive
- ER/PR negative, aneuploid
Paget’s Disease of Breast
- from excretory ducts and extends into skin of nipple/areola
- assoc DCIS/Invasive
- 50% underlying lump/mass
- Sir James Paget 1874
- Large cells with clear cytoplasm, nucleoli and abundant mucin (PAS Strain)
Ductal Carcinoma NOS
- most common type (80%) scirrhous
- penetrative (crab-like-cancer)
- calcification
- tumor may be fixed to the chest wall
- tubule formation, Nuclear pleomorphism and number of mitoses: MBR grading
Lobular Carcinoma
- 10% of all breast cancers
- 20% bilateral, often multicentric
- mets to CSF, BM, GIT, Serosal surfaces, ovary, uterus
- mass lesion may not be present
- single (Indian) file/targetoid, usually low grade appearance, signet ring cells
- morphologic variant forms
Inflammatory Carcinoma
- clinical diagnosis
- enlarged edematous breasts
- aggressive - need aggressive Rx
- Peau d’orange-lymphatic occlusion-thickened skin
Colloid Carcinoma
- “mucinous cancer”
- older women-slow growth
- better survival than ductal (12+ years after therapy)
- large lakes of mucin
Tubular Carcinoma
- 2-6% of all malignant tumors
- well differentiated-very favorable prognosis
- avg age 50 yrs(younger than ductal)
- good prognosis even with lymph node +
- 75% tubules (angulated)
Angiosarcoma
- usually younger women or older women (sp radiation)
- poor prognosis
- anastomosing vascular channels lined by atypical cells
- low and high grade
Carcinoma in Males (breast)
- 1% the rate of women (10% in Egypt)
- similar risk factors as women
- usually painless subareolar mass
- advanced stage presentation
- prognosis same as women when stage-matched
